Aim: the aim of this study was to evaluate the effect of botulinum toxin type A on structure, ultrastructure and immunohistochemical localization of E-cadherin in the rat submandibular salivary gland. Method: Forty female albino rats were used and divided into 2 groups. Group I injected subcutaneously by 2.5 U botox in the area of right side gland while the left side used as the control and then divided into 2 subgroups. Group II: right side gland was injected intraglandularly by 2.5 U botox, while the left gland used as the control and then divided into 2 subgroups. Results: injection of botox into submandibular glands for 14 days and 28 days resulted in structural and ultrastural changes in these glands, such alterations were more aggravated with the intraglandular injection. Immunohistochemical results revealed no significant difference in E-cadherin optical density between these subgroups. Conclusion: Botox could be considered as a therapeutic approach for sialorrhoea but yet concerns should be taken into consideration for its adverse effects on submandibular salivary glands.